In a recent study published in JAMA Network Open, researchers investigated the age of gestation associated with optimal perinatal outcomes among in-term single-infant pregnancies conceived using infertility therapies.

They assessed the time in pregnancy at which the continued risks of miscarriage were ideally matched with the risks of postnatal illnesses and infantile mortality.

Background

Pregnancies conceived using infertility therapies face elevated perinatal risks, including stillbirths, perinatal mortality, and low birth weight.

Assisted reproductive technology (ART)-induced pregnancies have no recommended delivery timing, making it crucial to balance these risks with neonatal morbidity and infantile mortality. The most appropriate delivery timing is unclear, possibly due to conception mode or underlying conditions requiring ART.

About the study

In the present retrospective cohort study, researchers investigated the age of gestation at which delivery is related to the best perinatal outcomes for within-term single pregnancies conceived using infertility therapies.

The study utilized deidentified birth and mortality information between 1 January 2014 and 31 December 2018 for United States (US) residents provided by the National Center for Health Statistics (NCHS). The team included singleton infants conceived using infertility therapies delivered between weeks 37 and 42 of gestation (at term).

Deliveries before 37 weeks or after 43 gestational weeks and multiple pregnancies with histories of congenital anomalies, unknown infertility therapy, preeclampsia, pregestational hypertension or diabetes, and gestational hypertension were excluded from the analysis.

The team analyzed data between 22 July 2022 and 24 June 2023. The exposure variable was the gestational week at delivery, ranging between weeks 37 and 42, and the primary study outcome was to uncover the optimum delivery timing.

The optimal delivery timing was based on the delivery risk (the composite of postnatal morbidity and infantile mortality rates at a particular gestational week among every 10,000 pregnancies) and was comparatively assessed with the delivery risk in the following gestational week based on the rate of stillbirths during the week among every 10,000 pregnancies and the postnatal morbidity and infantile mortality rates in the following gestational week among every 10,000 infants.

The stillbirth, postnatal morbidity, and infantile mortality rates were compared weekly. Postnatal morbidity was assessed based on Apgar scores of ≤3 at 5 minutes, ventilation requirements for ≥6 hours, seizures, and neonatal intensive care unit (NICU) admission.

Infertility treatments included fertility-enhancing medications, intrauterine insemination, artificial insemination, and ART use [in vitro fertilization (IVF), zygote intrafallopian transfer, and gamete intrafallopian transfer]. Gestational age was determined using the best obstetric estimate in birth records, based on the most recent menstrual period and various clinical and ultrasonographical parameters.

Results

The 340,728 infants conceived using infertility therapies corresponded to a 1.7% prevalence rate, in line with an increase in infertility treatments among US residents.

After excluding: 99,338 deliveries before week 37 or after week 42 of gestation; 37,457 multifetal pregnancies; 8,295 pregnancies with pregestational hypertension or diabetes; 16,429 pregnancies with gestational hypertension; and 761 pregnancies with congenital anomalies in the fetuses, 178,448 single-infant at-term pregnancies with infertility therapy were analyzed.

Of the 178,448 singleton-term pregnancies, the mean maternal and gestational ages were 34 years and 39 weeks, respectively, and 130,786 (74%) were White of non-Hispanic ethnicity. Stillbirth and infantile mortality rates were 0.1% (248 infants) and 0.1% (128 infants), respectively.

In comparison to spontaneous pregnancies, those conceived using infertility therapies had higher percentages of non-Hispanic White individuals, individuals aged 35 years and above, nulliparity, and preterm deliveries (PTDs).

Among pregnancies conceived using infertility therapies, neonatal birth weight was lower overall, and the small gestational age rate was higher in the stillbirth and infant mortality groups versus the live birth group (28.2% and 23.4% versus 8.3%).

Among Hispanic patients, the stillbirth and infantile mortality risks were 11.7% and 10.9%, respectively, and among non-Hispanic Black patients, the corresponding rates were 6.1% and 5.5%, respectively. Among non-Hispanic White patients, stillbirth and infantile death rates were 68.2% and 67.2%, respectively.

Delivery risk in the following gestational week was lower compared to that at week 37 (628 versus 1,005 among every 10,000 newborns) and week 38 (483 versus 625 among every 10,000 newborns).

The delivery risk in the following gestational week significantly exceeded that at 39 weeks (599 versus 479 among every 10,000 newborns) and showed non-significance at week 40 (639 versus 594 among every 10,000 newborns) and week 41 (701 versus 633 among every 10,000 newborns).

Among pregnancies conceived using infertility therapies, the relative risks (RRs) of delivery in the specified gestational week versus the following week were lowest at weeks 37 (RR: 0.6) and 38 (RR: 0.8) of gestation. At and after week 39 of gestation, the RR of delivery in the following versus specified gestational week exceeded the delivery risk (RR: 1.3).

In the pregnancies, the death risk for delivery in the specified gestational week versus the following week was higher at week 38 (RR: 1.7), week 39 (RR: 1.6), and week 40 (RR, 2.5) of gestation. Likewise, among pregnancies conceived using ART, the composite delivery risk in the following gestational week exceeded the delivery risk at week 39 (RR: 1.3).

The mortality risk at delivery in the following gestational week was not significantly higher compared to that at week 38 (RR: 1.6) and was significantly higher after week 39 (RR: 2.2) and week 40 (RR: 2.5) of gestation.

Overall, the study findings showed elevated risks of detrimental perinatal outcomes concerning pre- and post-term delivery among single infants birthed using infertility therapies. The study findings provide an evidence-based recommendation for delivery at week 39 of gestation for pregnancies conceived using infertility treatments that are not indicated for earlier delivery.